Treponema denticola does not induce production of common innate immune mediators from primary gingival epithelial cells.
It has been hypothesized that the neutrophil chemoattractant interleukin-8 (IL-8) forms a gradient in the oral cavity, with the highest concentration of IL-8 produced closest to the bacterial biofilm. In periodontitis, this gradient is disrupted, impairing neutrophil chemotaxis to diseased sites. Treponema denticola is prominently associated with periodontal disease, yet little is known about its ability to modulate the production of inflammatory mediators by epithelial cells. Others have shown that dentilisin, the major outer membrane protease of T. denticola, degrades IL-8 in vitro. We now provide evidence that T. denticola also fails to induce IL-8 production from primary gingival epithelial cells (PGEC). The lack of IL-8 production is not explained by IL-8 degradation, because a protease mutant that does not degrade IL-8 does not induce IL-8 production with these stimuli either. The lack of innate immune mediator production may be a more global phenomenon because T. denticola fails to induce IL-6 or intercellular adhesion molecule 1 production from PGEC. T. denticola also fails to induce transcription of IL-8 and human beta-defensin-2 messenger RNA. The lack of immune mediator production is not explained by the failure of T. denticola to interact with Toll-like receptor 2 (TLR-2), as T. denticola stimulates nuclear factor-kappaB nuclear translocation in TLR-2-transfected HEK293 cells. Not only can T. denticola degrade the IL-8 present in the periodontal lesion, but this organism also fails to induce IL-8 production by PGEC. The lack of an epithelial cell response to T. denticola may contribute to the pathogenesis of periodontitis by failing to trigger chemotaxis of neutrophils into the periodontal pocket.
Brissette
C A
CA
Department of Pathobiology, University of Washington, Seattle, WA, USA.
Pham
T-T T
TT
Coats
S R
SR
Darveau
R P
RP
Lukehart
S A
SA
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D005881:Gingiva / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D048373:Treponema denticola / Q000276:immunology*; D014211:Treponemal Infections / Q000276:immunology*
D015850:Interleukin-6; D016209:Interleukin-8; D051195:Toll-Like Receptor 2; D018799:Intercellular Adhesion Molecule-1